The mission of the proposed ACISR is to produce and disseminate comprehensive interventions that effectively target the complex clinical and social factors contributing to late-life depression, minimize the splintering of health care, and can be implemented under the current health reimbursement system. The rapid increase of older persons (73% increase is anticipated in US by year 2020) and the diseases and disabilities complicating their care make geriatric research a national priority. We focus on late-life depression because it is the leading cause of disability, increases medical morbidity and mortality, causes suffering, family disruption, and increases the cost of care. We propose a challenging program that expands our studies on clinical, psychosocial, and biological predictors of depression treatment outcomes and uses these findings and our clinical experience to develop interventions personalized at the patient and the setting level with the goal to preempt adverse consequences of late-life depression. To maximize our impact we will work both in settings in which most depressed elders receive care (primary care) and in settings serving elders with special clinical (disability) and social needs (poverty). To shorten the road from discovery to practice we plan to do most of this work in the community and together with our community partners. Our community partner will be the Westchester Geriatric Mental Health Coalition, which consists of medical practices, community mental health clinics, home healthcare agencies, rehabilitation hospitals, and government organizations who share our concerns. We propose to use Westchester County as an incubator of novel interventions, which we will further test at a national level in order to establish their public health significance. We are confident that we can meet the challenges of this work because of: 1. Our organizational experience in integrating research, methodology, community, and training activities into a cohesive, seamlessly-working system; 2. our research structures for ethics, scientific and logistic support, and training of staff; 3. our know-how, history and explicit plans in developing sustained partnerships with community agencies and learning from them; 4. our expertise in research methods development; and 5. our record and commitment to fostering the development of new investigators that will continue to invigorate our field. This application proposes a model of research development that can rapidly translate clinical, psychosocial, and biological findings into personalized interventions, shorten the way from discovery to community practice and benefit many depressed seniors, including those with severe pathology and limited resources who are neglected by traditional research.